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Background: Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post-T-DM1 treatments is currently lacking. We evaluated the effectiveness of post-T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer.Methods: In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post-T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken.Results: Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8-6.9) months, 5.6 (4.6-6.4) months, and 22.8 (18.2-32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8-56.7) and 23% (15.1-31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months.Conclusions: In the real-world setting in Japan, several post-T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings.Trial Registration: UMIN000038296 ; registered on 15 October 2019. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the cost-effectiveness of replacing standard intravenous therapy (taxane) with oral S-1 therapy for first-line metastatic breast cancer treatment.Methods: This cost-effectiveness analysis was based on data from a randomized phase III trial (SELECT BC). As cost-effectiveness was a secondary endpoint of the SELECT BC trial, some of the randomized patients participated in an EQ-5D survey (N = 391) and health economic survey (N = 146). The EQ-5D responses, claims, and prescription data were collected for as long as possible until death. The expected quality-adjusted life years (QALY) obtained from each treatment were calculated using patient-level EQ-5D data, and the expected cost was calculated using patient-level claim data. The analysis was performed from the perspective of public healthcare payers.Results: The estimated EQ-5D least-square means and 95% CI up to 48 months were 0.764 (95% CI, 0.741-0.782) and 0.742 (95% CI, 0.720-0.764) in the S-1 and taxane arms, respectively. The expected QALY was 2.11 for the S-1 arm and 2.04 for the taxane arm, with expected costs of JPY 5.13 million (USD 46,600) and JPY 5.56 million (USD 50,500), respectively. These results show that S-1 is cost-saving. According to probabilistic sensitivity analysis, S-1 was dominant with a probability of 63%. When the willingness to pay (WTP) value was JPY 5 million (USD 45,500) per QALY, the probability of being cost-effective was 92%.Conclusions: Our results show that the introduction of oral S-1 therapy for metastatic breast cancer is highly likely to be cost-effective.Trial Registration: UMIN CTR C000000416 . Registered on May 10, 2006. [ABSTRACT FROM AUTHOR]

Background Evidence of eribulin therapy for metastatic breast cancer ( MBC) in clinical practice is not well documented. Methods We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital. Results The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m2, and 75%, respectively. One patient achieved a complete response, ( CR) six a partial response ( PR), eight stable disease ( SD) and 14 patients exhibited progressive disease. The objective response rate ( ORR: CR + PR) was 24.1%, and the clinical benefit rate ( CBR: CR + PR + SD) was 51.7%. The median progression-free survival was 90 days (95% confidence interval [ CI] 67-126) and median overall survival was 264 days (95% CI 198-357). In patients who previously received 2-4 regimens, the ORR was 28.5% and the CBR was 57.1%. In patients who received 5-12 regimens, the ORR was 20% and the CBR was 45%. Chemotherapy was administered to 20 patients (69%) after eribulin administration, and the median overall survival rate of cases that achieved greater than a PR was 1088 days. The most frequent treatment-related grade 3/4 adverse events were neutropenia (55.2%), and febrile neutropenia (20.1%). Grade 3 peripheral neuropathy occurred in 13.8% of patients, but was not exacerbated even if present before treatment. Conclusion Eribulin is effective for MBC patients who have received multiple chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior therapy. [ABSTRACT FROM AUTHOR]

Background: With the widespread use of orally administered anticancer agents, self-management by cancer patients is inevitable, and adherence to medication is becoming the centre of interest in oncology. Methods/Design: This mixed-method study is a two-phased approach with a combined quantitative and qualitative design. In the first phase, we will conduct a prospective randomised controlled study to assess the effects of a nurse-led medication self-management programme for patients receiving oral anticancer treatment. Patients with metastatic breast cancer, who have been newly prescribed an oral chemotherapy or a targeted therapy agent will be enrolled in the study. The participants will be randomly assigned to either the medication self-management support programme group (intervention group) or the conventional care group (control group). This will be an open-label study; therefore, neither the patients nor the nurses will be blinded. Nurses will provide patients in the intervention group with information by using the teach-back method, help patients set a goal based on their preferences, and solve problems through follow-up counselling. The primary outcome measure is adherence to medication, to be measured on the basis of the medication possession ratio (MPR), which is the ratio of the number of days of medication supply to the total days at a specified time interval. We hypothesize that the intervention group will have an MPR of ≥90 % that is significantly higher than that of the control group. Secondary outcome measures include self-efficacy, quality of life, psychological distress, severity and interference of symptoms, patient satisfaction, emergency department visits, and hospital admissions. In the second phase, we will conduct focus-group interviews with intervention nurses, and perform a content analysis to understand their role and challenges these nurses will face in the programme while improving patients' medication adherence. Discussion: The present study will be the first Japanese study to evaluate the effects of medication self-management support provided by nurses to patients with metastatic breast cancer who are receiving oral anticancer treatment. The study is characterised by a unique patient-centred approach aiming to help patients manage their medication based on their needs and preferences, with both quantitative and qualitative evaluations. The findings will contribute to the facilitation of medication management in cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Capecitabine and S-1 are orally administered fluorinated pyrimidines with high-level activity against metastatic breast cancer (MBC). This randomized, multicenter, phase II study compared the activities and safeties of the oral fluoropyrimidines, capecitabine and S-1, in breast cancer patients. Methods: Patients with MBC were randomly assigned to receive capecitabine 825 g/m twice daily on days 1-21 every 4 weeks or S-1 40-60 mg twice daily, according to body surface area, on days 1-28 every 6 weeks. The primary endpoint was progression-free survival (PFS). Results: A total of 142 patients were enrolled and randomized to either capecitabine ( N = 73) or S-1 ( N = 69). Median PFS (progression-free survival) was 1.2 years for capecitabine and 1.3 years for S-1, with a hazard ratio (S-1/capecitabine) of 0.85 (95 % confidence interval [CI] 0.52-1.38) ( P = 0.48 by log-rank). The confirmed objective response rates were 24.0 % for capecitabine and 23.1 % for S-1 ( P = 0.938). The most common treatment-related adverse events were grade 1-2 in intensity. Thrombocytopenia (S-1: 9.2 %, capecitabine: 1.4 %; P = 0.040) and nausea (S-1: 26.2 %, capecitabine: 14.1 %; P = 0.079) were more frequent in the S-1 group, while hand-foot syndrome occurred more often in the capecitabine group (S-1: 10.8 %, capecitabine: 25.4 %; P = 0.029). Conclusions: The results of the current study demonstrate that both S-1 and capecitabine are effective and well-tolerated treatments in patients with MBC, while their adverse events were different. They are both convenient, orally administered drugs, making them attractive agents for use in outpatient treatment. [ABSTRACT FROM AUTHOR]

Objective: A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Methods: Escalating doses of CPT-11 (80-120 mg/m2) were administered on days 1 and 15. Capecitabine was administered at a fixed dose of 1,657 mg/m2/day for 21 consecutive days, followed by 7 days of rest. We treated 3-6 patients at a particular dose level until the MTD was determined. Results: Twenty patients were treated. The MTD was determined to be 100 mg/m2, as 3 of 6 patients developed dose-limiting toxicities, grade 3 leukopenia, neutropenia, photophobia, fatigue and diarrhea. The RD for the phase II study was thus determined to be 90 mg/m2. The response rate was 41.7%. Conclusions: Combination therapy with CPT-11 and capecitabine was well tolerated with a promising response rate for MBC that had been treated previously with anthracyclines and taxanes. A multi-center phase II study is warranted to evaluate the efficacy and safety of this combination therapy with pharmacokinetic assessment. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Anthracycline and taxane resistance is a key issue in the treatment of metastatic breast cancer (MBC), particularly in Asian patients who often present with advanced disease. The objective of this study was to investigate the efficacy and safety of ixabepilone monotherapy in Japanese patients with taxane-resistant MBC previously treated with anthracycline. Patients and methods: Japanese patients with taxane-resistant MBC previously treated with anthracycline were treated with 40 mg/m ixabepilone every 3 weeks. Primary endpoint was overall response rate. Secondary endpoints included duration of response, time to progression (TTP), and safety. Results: Fifty-two patients were treated with ixabepilone. Overall response rate was 11.5 % (95 % confidence interval 4.4-23.4), stable disease rate was 38.5 %, duration of response was 3.6 months (range 2.4−5.3 months), and TTP was 2.8 months (range 0.7-8.1 months). The most frequent grade 3/4 toxicities were neutropenia (82.7 %), leukopenia (75 %), myalgia (19.2 %), and peripheral neuropathy (19.2 %). Conclusion: Ixabepilone monotherapy was effective and toxicities were manageable in this phase II study of Japanese patients with taxane-resistant metastatic breast cancer previously treated with anthracyclines. [ABSTRACT FROM AUTHOR]

With the development of the CellSearch System, it has become possible to measure circulating tumor cell (CTC) levels with high reproducibility, and the CTC test is currently being used clinically for patients with metastatic breast cancer in the United States. It is imperative that the clinical significance of the CTC test also be examined in Japan. Using the CellSearch System, CTC levels were evaluated in 57 healthy individuals and patients with benign breast disease; 30 patients with primary breast cancer (stages 1–3); and 38 patients with metastatic breast cancer. First, the relationship between CTC levels and the presence of metastasis was examined using a cutoff score of 2 CTCs per 7.5 ml whole blood. Then, the patients with metastatic breast cancer were divided into two groups, using a cutoff score of 5 CTCs per 7.5 ml blood, and progression-free survival (PFS) and overall survival (OS) were compared in the two groups. When the clinical cutoff score was set at 2 CTCs per 7.5 ml blood, 0% of the healthy individuals and patients with benign breast disease (0/57), 3.3% of the patients with primary breast cancer (1/30), and 50% of the patients with metastatic breast cancer (19/38) were identified as as having 2 CTCs per 7.5 ml blood. Additionally, with a cutoff score of 5 CTCs, 11 patients were reported to have 5 or more CTCs and both PFS ( P = 0.0036) and OS ( P = 0.04) were worse for this patient population than for the population with fewer than 5 CTCs. As concluded in a similar clinical trial in the United States, for patients with breast cancer, measuring CTC levels can be both an accurate indicator of metastases and an important measure of patient prognosis. [ABSTRACT FROM AUTHOR]

The PALOMA2/3 trials demonstrated prominent efficacy of combination therapy of palbociclib (PAL) and endocrine therapy (ET) compared with monotherapy. PAL was approved for metastatic breast cancer in Japan in 2017. We evaluated the efficacy and safety in practice after approval of PAL in Japan. We retrospectively reviewed patients who newly received PAL at Aichi Cancer Center after Dec 2017. The patients were classified by treatment-line and assessed as follows; clinical benefit rate (CBR) defined as the rate of clinical PR, CR and long SD (more than 6 months) based on physician's judgment, time to failure (TTF) defined as the duration time of PAL, prior ET response, and adverse events (AEs). TTFs were figured with swimmer's plot by treatment-line, PAL doses (125, 100, 75mg/day). Between Dec 2017 and Oct 2018, 64 patients were eligible. Median age was 62.5 (37-82). Forty-one patients (64%) had visceral metastasis. PAL was administered for 1st to 3rd line (early-line group) in 52% (n = 33), and for more than 4th line (late-line group) in 48% (n = 31). Combination ETs were aromatase inhibitors (n = 27, 42%), fulvestrant (n = 35, 55%), and tamoxifen (n = 2, 3%). Prior ET was sensitive in 59% (n = 33). The dose reduction was needed in 62% (100mg; n = 19, 75mg; n = 21). Twenty-eight patients (43.8%) were continuing PAL. Overall CBR was 38%. By treatment line, CBR was 51.6% in the early-line group, and 22.6% in the late-line group. Median TTF was 4.6 months (0.2-10.2). There were no significant differences of TTF by treatment-line, prior ET response, and PAL doses. The grade 3-4 hematological toxicity, such as neutropenia and anemia, were observed in 83% (n = 53). Stomatitis, nausea, and fatigue were common, but most of them were grade 1-2. No patients discontinued PAL due to AEs. In the clinical setting, PAL was given in many late line-patients who were not eligible for the PALOMA2/3 trials. Its efficacy was not sufficient, although it was feasible. [ABSTRACT FROM AUTHOR]